FDA warns Boehringer-Ingelheim over cGMP failings


Inspection finds foreign particles in lots of APIs and finished drugs

The FDA has sent a warning letter to Boehringer-Ingelheim over cGMP violations at its active pharmaceutical ingredient (API) and finished pharmaceutical manufacturing facility at Ingelheim am Rhein, Germany, following an inspection in November 2012.

On the API side, the FDA said Boehringer Ingelheim’s quality unit had failed to thoroughly investigate critical deviations in the manufacturing of ingredients between 2008 and 2009.

The company failed to determine the source of foreign particles and continued to use lots of APIs that had been identified as contaminated with foreign particles, the Agency said.

‘We are concerned about your inability to prevent the presence of foreign particles in your APIs and the adequacy of actions taken to address the situation,’ said Michael Smedley, Acting Director of the Office of Manufacturing and Product Quality at the Center for Drug Evaluation and Research at the FDA in a letter to Gerhard Gigli, Senior Vice President of Boehringer-Ingelheim Pharma.

With regards to finished drug product, the FDA said Boehringer-Ingelheim failed to reject multiple batches of capsules that were contaminated with foreign particles ranging in size and weight from approximately 200 microns to approximately 5mm, and from 0.4 micrograms to approximately 9mg, respectively.

The FDA also said it disagreed with Boehringer-Ingelheim’s decision to use the API because the contaminated batches met the final specifications.

‘Use of appropriate manufacturing, controls, quality standards, and systems for investigations of atypical events (e.g., contamination) are all essential parts of a robust quality system,’ the Agency said. ‘Quality cannot be added into a product after it has been manufactured.’

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In addition, the firm failed to determine the cause of an out-of-specification lot of its Spiriva HandiHaler, which ‘failed the uniformity of delivered dose test specification’, according to the FDA.